Anorexia nervosa is a complex eating disorder characterized in part by hypophagia, disorganized eating patterns, body weight loss, hyperactivity, and a dysregulation of the hypothalamic-pituitary-gonadal axis. About 90% of diagnosed cases involve women. Therapeutic treatment of the symptoms of anorexia nervosa is limited due to our lack of understanding of the multiple factors underlying this complex disorder. Animal studies have shown that female rats maintained on a food restriction schedule and given free access to running wheels display hypophagia, rapid body weight loss, increased running wheel activity, and a disruption of ovarian reproductive function. Because these symptoms are similar to the symptoms of anorexia nervosa, this paradigm has been used as an animal model of anorexia nervosa. The aim of this proposal is to use this animal-based model to investigate (a) the spontaneous feeding patterns of female rats with activity-based anorexia, (b) whether estradiol modulates susceptibility to activity-based anorexia, and (c) the patterns of meal-stimulated neuronal activation in female rats with activity-based anorexia: Female rats will be housed in custom-designed cages that permit the continual monitoring of spontaneous feeding and running wheel activity. The effects of estradiol on the development of activity-based anorexia will be investigated in ovariectomized rats with and without estradiol replacement. Finally, c- Fos immunohistochemistry will be used to visualize changes in meal- stimulated neuronal activity. This research will provide novel information regarding the behavioral, hormonal, and neural substrates of activity-based anorexia and will, therefore, provide a foundation for future experiments investigating the mechanism underlying activity- based anorexia. A long-term goal of this research effort is to identify the neurochemical substrate underlying anorexia nervosa in the hope that this may lead to the development of more effective pharmacotherapeutic treatments and intervention programs.